Senescence is an unavoidable phenomenon for animals. Progress in life science leads to advances in studies on senescence, revealing senescence events at the levels of an individual and of organs, tissues, cells, and genes, and in addition, cooperative working of nerves and vessels, immune regulation, and substances of various types, such as hormones and regulatory factors, that provide their linkage, and yet the detailed mechanism of senescence has not become revealed. However, there have been found clues for elucidating the mechanism of senescence, and it has become widely known that in animals, such as nematodes, fruit flies, rats, mice, and monkeys, dietary caloric restriction provides an effect of extending their longevity (Non-Patent Literatures 1 to 4). It is estimated that the energy metabolism in mitochondria is involved in this context. In addition, calorie restriction mimetics have also been sought with the view of retarding senescence and extending longevity (Non-Patent Literature 5). The relation between insulin and growth factor (IGF-1) signals and longevity has also been found as a common signaling pathway in nematodes, fruit flies, and mammals (mice) (Non-Patent Literature 6). Further, there have been found results that resveratrol, a low molecular weight component contained in red grapes, is expected to have an action of retarding senescence and an effect of extending longevity (Non-Patent Literature 7), and investigations are being carried out to seek for analogous substances (Non-Patent Literature 8). Recently, sirtuins have been found to have an enzymatic activity of deacetylation of histones and to be involved in extending longevity, and are expected to be associated with senescence as clues for further studies. Small molecule modulators of sirtuins have also been found (Non-Patent Literature 9).
It would be difficult to stop senescence symptoms that occur with aging, but one wants to retard the onset of senescence symptoms and in addition, to extend his/her longevity. However, it is estimated that more than one gene and process are responsible for the cause of these senescence symptoms (Non-Patent Literature 10). For this reason, testing using animal individuals is required for evaluation of the delay of the onset of senescence symptoms or the prolongation of longevity. In addition, model animals with a short generation time are necessary for examination and investigation on longevity. Such model animals include nematodes, fruit flies, and mice. Among these, mice are mammalian and have a longevity of about two to three years even in the case of normal mice, and therefore, can be used to estimate effects on senescence and longevity in a relatively short period of time. Mice of the SAM-P line, which is a senescence accelerated model mouse line that was found in mice of the AKR line at an animal experiment facility at Kyoto University, have a longevity of about 1.5 years and display various symptoms characteristic of senescence, and thus are used widely in studying senescence in comparison with SAM-R1 mice, which are of a normal type of the same line. Mice of these types have been passaged and propagated by and are commercially available from the Council for SAM Research, and methods for evaluating senescence symptoms have also been standardized by the Council for SAM Research. As the standardized senescence indexes, use is made of abnormal or slow behavior, eye symptoms (periocular erosion, cloudycornea, cataract, and the like), hair loss, senescence symptoms of the skin, such as the coat of hair, and backbone curvature. On the other hand, the prolongation of survival, which is an index of retarded senescence, is not included in the standard evaluation indexes defined by the Council for SAM Research.
Symptoms similar to those in the case of senescence have also been observed in damage caused by irradiation of radiation (Non-Patent Literature 11). It has been reported by Ito et al. that damage was caused in mucosal stem cells of the small intestine of mice which had been irradiated with 6 to 14 grays of X-ray radiation, while mice which had received miso (a Japanese fermented soybean paste) in combination with feed had less damage of stem cells of crypts of the small intestine (Non-Patent Literature 12). However, Ito et al. has not given any report on senescence symptoms or the survival rate of mice. It has been reported that using a similar evaluation system, Manda Koso, which is a plant fermentation food, was effective in the prevention of damage of mucosal stem cells of the small intestine of X-ray irradiated mice (Non-Patent Literature 13), but there was no report on the retardation of senescence symptoms or prolongation of the survival of mice by Manda Koso.
Furthermore, it has been reported that in cases where senescence accelerated model mice of the SAM-P1 line were employed, coenzyme Q10 and its reduced form exerted an effect of preventing senescence symptoms (Non-Patent Literature 14). In comparison with mice without added CoQ10, mice receiving CoQ10 exhibited a significant effect of preventing senescence in terms of eye symptoms, skin symptoms, backbone curvature, and total symptom score, and yet, did not have an extended longevity. It has also been reported that when effects of soybean proteins SPI and casein on senescence were compared, there was observed no difference in the degree of senescence between for both proteins, while SPI was found to have a survival prolonging effect (Non-Patent Literature 15).
For sirtuins involved in senescence, it has been reported that their enhancement or suppression is caused by Chinese medicines and others, but they have not been tested as to whether they extend longevity. On the other hand, resveratrol, which is contained in red grapes, has been reported to extend the longevity of fruit flies and mice.
Besides the above, there have been many reports on retarding senescence or extending longevity. For example, it has been disclosed that application of a substance inhibiting the expression or function of a gene encoding G protein γ subunit 11 makes it possible to inhibit cellular aging (Patent Literature 1). In addition, it has been reported that alkyl resorcinols having a specified structure have an action of activating sirtuins and an action of retarding senescence, and exhibit an effect of extending the longevity of individuals (Patent Literature 2). Furthermore, it has been disclosed that royal jelly, heterocyclic compounds with a specified structure, resveratrol, an extract from grape leaves, active carbon, an extract from Chinese redbud (Cercis chinensis), curcuminoids, a kudzu (Pueraria lobata) extract, and others exhibit an action of preventing senescence, an action of extending longevity, and the like (Patent Literatures 3 to 10).
However, the fact is that there are little reports on foods, medicaments, and others exerting on mammalian animals both an effect of delaying the onset of senescence symptoms and an effect of extending longevity as an extension of senescence.